Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver

Abstract

Podoplanin, which is immunoreactive to D2-40 antibody, is reportedly expressed in lymphatic vessels in nonneoplastic tissues, and also in vascular and non-vascular tumors. However, its expression in non-neoplastic and neoplastic liver tissues has not been well documented. In this study, we examined podoplanin expression in specimens from 10 normal livers and 73 cases of liver tumors: hemangioma (16 cases), epithelioid hemangioendothelioma (9 cases), angiosarcoma (4 cases), angiomyolipoma (7 cases), hepatocellular carcinoma (11 cases), intrahepatic cholangiocarcinoma (11 cases), and metastatic liver cancer (15 cases). We compared levels of podoplanin and other endothelial markers (CD31, CD34, and factor VIII) in liver tumors. In the normal liver, podoplanin was expressed in lymphatic endothelium, nerve fibers, and mesothelium in the hepatic capsule, but not observed in any cells within hepatic lobules. Among liver tumors, podoplanin was specifically expressed in seven of nine cases (78%) of epithelioid hemangioendothelioma but not in other hepatic tumors. The expression of CD31, CD34, and factor VIII was observed in endothelial cells in all cases of hemangioma, epithelioid hemangioendothelioma, angiosarcoma, and angiomyolipoma with one exception, a case of epithelioid hemangioendothelioma which was without CD31 expression. Interestingly, the intensity of podoplanin expression was negatively correlated with the expression of CD34 and factor VIII. In conclusion, podoplanin would be useful as a diagnostic marker for epithelioid hemangioendothelioma in liver tumors.

Lymphatic Endothelial Differentiation in Pulmonary Lymphangioleiomyomatosis Cells

“…Despite their use of D2-40 at a 100-fold lower concentration than in our study, the micrographs presented show faint but definite staining with D2-40 in most of the LAM-like cells (Hansen et al 2007). Such mild immunopositivity was likely regarded as nonspecific staining, but D2-40 antibodies produce a clear background and are highly specific to lymphatic endothelium, as demonstrated by the complete negativity for D2-40 in the LAM-like cells of AMLs studied here and previously by others (Fujii et al 2008;Bonsib et al 2009;Xian et al 2011). Moreover, the absence of D2-40 in all but the lymphatic endothelium of the AMLs in our study confirms that our experimental protocol did not result in overstaining of the LAM specimens.…”

High-level expression of podoplanin in benign and malignant soft tissue tumors: Immunohistochemical and quantitative real-time RT-PCR analysis

“…and other vascular lesions, such as epithelioid hemangioendotheliomas of the head, neck and liver (25,26), and hemangioblastomas of the CNS (27). Membranous and cytoplasmic immunoreactivity for podoplanin was detected in 86-100% of epithelioid mesotheliomas, respectively, whereas podoplanin is invariably negative in lung adenocarcinomas (14).…”

D2-40 Immunoreactivity of Lymphatic Vessels Endothelium and Representation of Lymphatic Vessels in the Liver of Human Fetuses of Different Gestational Age

“…In addition to the use of D2-40 molecule as a marker of endothelial cells in lymph vessels, there has been evidence of the expression of its receptorpodoplaninin certain tumors of the liver as well (hemangioma, epithelioid hemangioendothelioma), so that D2-40 molecule, that binds to podoplanin, in addition to being adopted as a marker of lymph vessel endothelium, can be used as a diagnostic marker for epithelioid hemangioendotheliomas in the liver (20). …”

“…Endothelium is a common structural component of lymph vessels and sinusoids of the liver, but during embryonal development it differentiates into two morphologically and functionally different epithelial lines characterized by the expression of different molecules -endothelial cells in the liver sinusoids express, above all, CD31 and CD34 molecules (16,17), while endothelial cells of the lymph vessels express LYVE-1 (8,18,19) and D2-40 molecules (20,21).…”